During fertilization, sperm-cell-derived DNA can be found in the oocyte cytoplasm. In Immunity, Abe et al. identify NLRP14 as a negative regulator of the cytosolic nucleic-acid-sensing pathway expressed specifically in germline cells. Deletion of NLRP14 enhances induction of the cGAS–STING and RIG-I–MAVS pathways in response to various DNA and RNA in 293T human embryonic kidney cells with ectopic expression of the components of these pathways, while overexpression of NLRP14 has the opposite effect. Overexpressed NLRC14 interacts with the kinase TBK1 and induces its polyubiquitination and a decrease in TBK1 protein. A previously described mutant NLRP14 with a stop codon at amino acid 108 that is associated with spermatogenic failure does not interact with TBK1 and fails to inhibit the TBK1-dependent activation of the transcription factors IRF3 and NF-κB. NLRP14 is downregulated immediately after fertilization, which indicates that modulation of the nucleic-acid-sensing pathways is required for normal fertilization.
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Visan, I. Fertilization and nucleic acid sensing. Nat Immunol 18, 603 (2017). https://doi.org/10.1038/ni.3760
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DOI: https://doi.org/10.1038/ni.3760
